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Researchers Uncover New Factors Linked to Williams Syndrome

Written by AUFTAU on . Posted in Newsroom.

Findings may contribute to development of treatments to enable normal expression of genes essential for brain development in people suffering from the syndrome.

Williams syndrome is a relatively rare, multisystem genetic syndrome that causes disorders in brain development. A new study by the Tel Aviv University and Hebrew University found that abnormal processes lead to disruption in the expression of genes essential for brain development in people suffering from the syndrome. The researchers believe their findings may contribute to the future development of targeted treatments that will enable normal expression of the affected genes identified in the research.

Looking Beyond Chromosome 7

The research was led by Dr. Boaz Barak from the School of Psychological Sciences and the Sagol School of Neuroscience at Tel Aviv University and Dr. Asaf Marco from the Faculty of Agriculture, Food and Environment of the Hebrew University. Also participating in the research were Dr. Sari Trangle, Mr. Gilad Levy and Ms. Ela Bar from Dr. Barak’s laboratory, and Dr. Tali Rosenberg and Ms. Hadar Parnas from Dr. Marco’s laboratory. The research findings were published in the prestigious journal Molecular Psychiatry from the Nature publishing group.

 

“We wanted to examine whether the Williams Syndrome is also characterized by defects in the genomes contained in brain cells which prevent the proper expression of essential genes.” Dr. Boaz Barak

 

Dr. Barak: “Williams syndrome is a rare, multisystem genetic syndrome that includes disorders in brain development that lead to heightened social interactions, mental retardation, and other characteristic features. Past research has revealed that twenty-five genes are missing from the DNA on chromosome number seven of people with Williams syndrome, and the study of the syndrome to date has mainly focused on those missing genes and their functions.”

“We wanted to examine whether the syndrome is also characterized by defects in the genomes contained in brain cells which prevent the proper expression of essential genes. Specifically, we asked: ‘Is it possible that certain genes are not expressed properly in the brains of people with Williams syndrome due to the phenomenon of methylation – when a molecule known as a ‘methyl group’ is located on a certain gene that is present in the genome, preventing it from expressing itself properly?”.

To illustrate the phenomenon of the missing genes, Dr. Barak took an instruction book in which some of the pages were torn out. As a result of the missing pages, anyone following the instructions would make mistakes. Similarly, hiding some of the letters in the pages left in the book with a black marker would result in instructions being corrupted, just like methylation on an existing gene disrupts its expression.

Methylation is in many cases a normal mechanism in the cells of the body, as its role is to prevent expression of certain genes when appropriate. However, when there are disruptions in the correct application of methylation, the abnormal expression of the genes may lead to impairments in cell function, and subsequently cause damage to various organs, including to normal brain development.

 

Dr. Boaz Barak  from the School of Psychological Sciences and the Sagol School of Neuroscience at Tel Aviv University

Uncovering New Factors

The researchers examined human brain tissues taken from adults with and without Williams syndrome who died of causes unrelated to the syndrome and donated their brains to science.

“We focused on samples from the frontal lobe, the area of the brain that is responsible for brain functions such as cognition and decision-making,” Dr. Barak explained. “In a previous study, we located in this area damage to the characteristics of the nerve cells and the cells that support nerve cell activity in people with Williams syndrome. In this study, we examined all the genes in all the cells of the frontal lobe to determine whether there are genes in people with Williams syndrome that have undergone abnormal methylation processes, i.e., increased or decreased gene silencing compared to a brain with typical development.”

 

“We uncovered significant information about the defective expression of genes in people with Williams syndrome. While these genes are fully present in the genome of the brain cells, until now it was not known that these abnormally regulated genes are involved in the syndrome.” Dr. Asaf Marco.

 

The researchers found that indeed in people with Williams syndrome abnormal methylation does exist in this area of the brain, resulting in disruption of the normal expression of many genes related to the normal development of the brain’s neural functions, such as regulation of social behavior (people with Williams syndrome are known to be overly friendly), cognition, plasticity of the brain, and cell survival.

“We uncovered significant information about the defective expression of genes in people with Williams syndrome. While these genes are fully present in the genome of the brain cells, until now it was not known that these abnormally regulated genes are involved in the syndrome,” says Dr. Marco.

 

“Building on our findings, it will be possible to focus future efforts on the development of targeted treatments that will reach the disrupted sites that we identified in the study in order to ‘correct’ the defective expressions.” Dr. Boaz Barak

 

Next Step: Target Disrupted Sites

“In addition, one of our main findings is that the disruptions in methylation do not have to appear near the gene whose function is impaired, and sometimes the disruptions are located far away from it. This information is critical because it allows us to better understand the spatial organization of DNA and its effect on gene control.”

He adds that, “since we know of enzymes that are able to remove or add methyl molecules, the next challenge will be to precisely direct those enzymes to the disrupted sites identified in our research, with the aim of allowing the genes to be properly expressed.”

Dr. Barak concludes: “Our research revealed new factors related to the disabilities that characterize Williams syndrome. Instead of focusing on the effects of the missing gene, as has been done until now, we shed light on many more genes that are expressed in a defective manner. Building on our findings, it will be possible to focus future efforts on the development of targeted treatments that will reach the disrupted sites that we identified in the study in order to ‘correct’ the defective expressions.”

Lessons in Tolerance and DNA Extraction in Tel Aviv University’s Medical Labs

Written by AUFTAU on . Posted in Newsroom.

High school students on the autism spectrum were integrated for a whole semester in the research laboratories of TAU’s Faculty of Medicine.

A hugely successful pilot project was concluded in Tel Aviv University’s Sackler Faculty of Medicine, in which nine curious high school students on the autism spectrum from the Ahad Ha’Am School in Petah Tikva (a city in the Central District of Israel) were integrated in the University’s medicine labs for one semester. In the labs, the highschoolers experienced research and teamwork under the guidance of TAU medical students and doctoral students. Together, they programmed codes for research analyses, grew bacteria, extracted DNA, and other fascinating activities.

All good things come to an end, and a touching farewell ceremony was held on campus last week. Good news is, because of the project’s success there are now plans to expand the program to include additional School of Medicine labs.

Opening the Labs

The special project was launched by Sharon Naor, a TAU PhD graduate student of the Faculty of Medicine, and Prof. Karen Avraham, Dean of the Faculty, in collaboration with Kobi Malka, Director the of the “גדולים במדים” (“Big in Uniform”) program of the Lend a Hand to a Special Child association. Malka’s program typically works to integrate children on the autistic spectrum into the army.

The project consisted of two-hour sessions every week for an entire semester. Every week, the youth met with graduate and doctoral students who generously contributed their time and knowledge in seven different medical laboratories that were allocated for the project. 

 

Mutual contribution (from left to right): Lily Trossman and Dr. Moran Goren, who took part in the project together

 

“One of the [TAU] students told me during the semester: ‘I’m learning to be more tolerant and to listen to someone who thinks at a different pace. It doesn’t mean that the person is less talented than me.’ In other words: ‘I came to teach and left educated'” Dr. Sharon Naor

 

Came to Teach and Left Educated

“We thought it would be a good idea to introduce young people diagnosed on the autistic spectrum to the world of science, explains Dr. Sharon Naor. “We’re not talking about a day of fun, but to bring them inside some of Tel Aviv University’s many labs and let them be a part of what’s going on there for some time. Who knows, maybe the experience will inspire some of them to become scientists themselves one day,” he muses.

He is convinced that the sessions were mutually beneficial for the highschoolers and for the University students: “One of the graduate students told me during the semester: ‘I’m learning to be more tolerant and to listen to someone who thinks at a different pace. It doesn’t mean that the person is less talented than me.’ In other words, the student joined the project with the intention to teach and was surprised to leave the experience educated.” 

The Dean of Medicine agrees that both highschoolers and students benefitted from the project. Addressing the participants from her Faculty, Prof. Karen Avraham commended the students for dedicating their time to this project and added: “I believe that these two hours a week have nurtured something inside you as well, and that the project opens our hearts. I have no doubt that we will continue this wonderful project.”

 

“What helps build a better society are small human actions, the ability to pay attention to the needs of other people, and to look for ways to accommodate and to provide a suitable response.” Yael Bezalel Zhelezni

 

While We’re on the Topic of the Heart… 

“We work hard to prepare our students for the future by familiarizing them with various systems and institutions that they will encounter, such as the military system, the employment system… and this year we got the opportunity to introduce them to the academic system as well!” said Yael Bezalel Zhelezni, Director of the Ahad Ha’Am School, addressing TAU’s academic staff. She and her staff had witnessed the participating highschoolers’ great excitement about the lab sessions during the semester.

“What helps build a better society are small human actions, the ability to pay attention to the needs of other people, and to look for ways to accommodate and provide a suitable response. This project is a lesson in modesty, respect and friendship… and perhaps the most important lesson they will receive in their lives: how to be a person who sees the other and their needs (…) We are all different in some way or another.”

She noted that, “whereas the apparent target may be our young students, the real target of education in this project is society at large” 

Bezalel Zhelezni expressed her hope for the future generation of health professionals: “I hope, dear students, that these encounters will stay with you in the future, when you provide the most important care for humanity – medical care. And as for the lecturers among you: beyond producing talented new doctors, I hope that you will also pass on a sensitivity to this special group within our population. And that you will do so with pride.”

Featured Image: The project’s trainees, supervising students and Prof. Karen Avraham, Dean of the Faculty of Medicine

Medical Clowns – No Laughing Matter

Written by AUFTAU on . Posted in Newsroom.

Israeli researchers find that medical clowns contribute significantly to the achievement of medical therapeutic goals.

You see them stroll around in the hospitals’ toughest wards with their red noses, colorful clothes, and unwavering smiles, spreading laughter and cheerfulness wherever they go. They are the medical clowns: trained professionals whose goal is to change the hospital environment through humor. 

A new study tested and categorized the skills of medical clowns and found that their importance goes far beyond contributing to a patient’s good mood. The researchers identified 40 different skills of medical clowns, including establishing an emotional connection and creating a personal relationship with the patient, expressing the patient’s frustrations and difficulties to the medical staff, increasing the patient’s motivation to adhere to medical treatment, distracting the patient from pain, and creating a joyful atmosphere.

 

Medical clowns working alongside other therapists (Photo: The Dream Doctors Project, Medical Clowning in Action)

Not Just for Entertainment Purposes

The research was conducted under the leadership of Prof. Orit Karnieli-Miller, with Dr. Lior Rosenthal, both from the Department of Medical Education at TAU’s Sackler Faculty of Medicine, in collaboration with Ms. Orna Divon-Ophir, Dr. Doron Sagi, Prof. Amitai Ziv and Ms. Liat Pessach-Gelblum from the Israel Center for Medical Simulation (MSR). The study was published in Qualitative Health Research, a leading journal in the field of health.

The researchers show that not only do medical clowns help the patients and their family members, but also the medical team and the achievement of treatment goals.

Through use of different communication skills, clowns make it easier for the patient to cooperate with various treatments. The medical clowns work in a team with other therapists, know how to intervene and help whenever an argument or crisis should arise to advance treatment.

 

“From the moment they enter the room, the clowns form a bond with the patients, strengthen them, and give them power and status within the medical system.” Prof. Orit Karnieli-Miller. 

 

Decoding their “Secret Magic”

Studies conducted throughout the years have shown the clowns’ positive influence on the hospital environment through humor, as well as helping patients deal with pain. However, no studies have empirically mapped the skills they use and their therapeutic goals to help understand their “secret magic.” In addition, there was a lack of broad understanding of how clowns can help children, teenagers, and their parents in various challenging situations of distress and difficulty, as well as how they can help patients and medical teams achieve treatment goals. This lack of appreciation of the potential benefits of utilizing the services of medical clowns meant that patients and medical teams would occasionally be reluctant to cooperate with them.

As part of the new study, the researchers focused on qualitative, in-depth systematic identification of the skills of medical clowns through observation and analysis of their actions in challenging encounters with adolescents, parents, and medical staff.

 

Medical clowns help patients and medical teams achieve treatment goals (Photo: The Dream Doctors Project, Medical Clowning in Action)

The team analyzed videotaped sessions of medical clowns in various simulated situations and conducted in-depth interviews with expert medical clowns. The researchers identified 40 different skills used by the medical clowns to achieve four therapeutic goals:

1) building a relationship and connecting to the needs and desires of the patients

2) dealing with emotions and difficulties

3) increasing the patient’s motivation to adhere to the treatment plan

4) increasing the patient’s sense of control and providing encouragement to patients

The clowns examined in the study were trained and recruited by the “Dream Doctors Project”, a non-profit association that employs medical clowns as part of the paramedical system in Israeli hospitals, and trains them to work within multi-disciplinary teams. The Tel Aviv University researchers collaborated with the Israel Center for Medical Simulation (MSR), which created a simulation-based workshop focused on developing the skills of experienced medical clowns.

“From the moment they enter the room, the clowns form a bond with the patients, strengthen them, and give them power and status within the medical system,” explains Prof. Karnieli-Miller. “They do this through an initial connection to the patients’ voice, and even to the patients’ reluctance to implement therapeutic recommendations – an emotional connection that often results in the patient changing their position and cooperating with the medical staff.”

 

Providing the patient with an increased sense of control and courage to face their challenges (Photo: The Dream Doctors Project, Medical Clowning in Action)

According to Prof. Karnieli-Miller the medical system is hierarchical, and it is not always easy for patients to navigate. Therefore, one of the skills of medical clowns is to place themselves in the lowest position in the medical setting. By doing so, they empower the patients by giving them a sense of power and control, including the choice of whether to allow the clown to enter the room as well as to dictate the nature of the patient’s role vis-à-vis that of the clown. This provides the patient with an increased sense of control and courage to face their challenges.

The researchers emphasize that the clowns are very aware of the emotional difficulty associated with staying in a hospital and dealing with an illness. To help deal with these issues, the clowns sometimes distract the patient by using props, humor, and imagination. Other skills include allowing the patient to direct their frustrations towards them, away from medical staff or parents.

Depending on the situation the clowns may also use a comforting touch, soothing music, empathetic listening, or a reinforcing statement to provide an environment where the patient feels comfortable to express their feelings. A patient’s ability to gain legitimacy is important and is strengthened by the clowns.

 

Prof. Orit Karnieli-Miller

 

“Mapping the skills and goals of the medical clowns improves their understanding of their role and may help other health professionals appreciate their work methods and the benefits of incorporating these methods into their own practices when faced with similar challenges” Prof. Orit Karnieli-Miller.

 

Learning from Medical Clowns’ Methods

“Mapping the skills and goals of the medical clowns improves their understanding of their role and may help other health professionals appreciate their work methods and the benefits of incorporating these methods into their own practices when faced with similar challenges,” adds Prof. Karnieli-Miller.

“This research is important because it allows the clowns to enhance their training program and refine their diverse skills to achieve the various therapeutic goals appropriate for different patients, as well as helping health professionals collaborate with the medical clowns. If professionals in the healthcare field gain a clear understanding of how and when to cooperate with the medical clowns, they will be able to help patients overcome challenges, and at the same time they may be more tolerant of the clowns’ ‘disruption’ of the hospital care regimen. This appreciation of the clowns’ contribution will provide the clowns with the time and space to connect with patients and help and encourage patients to become more active participants in their treatment plan,” she concludes.

Featured image: Medical clown with happy customer (Photo: The Dream Doctors Project, Medical Clowning in Action)

Tel Aviv University’s First MedTech Hackathon Sets a High Bar

Written by AUFTAU on . Posted in Newsroom.

200 students from six different disciplines find practical solutions to burning challenges in Israeli medicine.

TAU’s first competition for medical innovation ended last weekend (January 11-13) with spectacular results. The TAU MedTech Hackathon, organized by four entrepreneurial students from Tel Aviv University’s faculties of Medicine and Engineering, included 200 students who participated alongside 120 mentors and 30 judges from Israeli medicine and hi-tech. They shared the common goal of finding solutions for today’s burning medical problems. 

Burning Challenges from Israel’s Medical Industry

TAU students from Medicine, Engineering, Computer Science, Bioinformatics, Neuroscience, and Sofaer Global MBA (the flagship global MBA program of the Coller School of Management) worked together in 34 interdisciplinary teams for over 40 hours to come up with practical solutions to critical issues as defined by selected Israeli organizations and hospitals. 

Among the problems: finding a technological solution for early detection of peripartum depression (depression occurring during pregnancy and/or after childbirth); providing remote healthcare to ease the burden on hospitals and individuals who are physically challenged; inventing a new and safe device for brain water drainage in cases of hydrocephalus (a life threatening condition in children), and more.

The participants were not left to their own devices: each team was assigned two mentors, one from the medical world and another from the technological world, each leader in their field. In addition, the participants could join lectures and TED-style talks by industry experts.

Among the 200 participants were 30 international students, eight of them from Sofaer Global MBA. “The hackathon was an amazing experience which allowed our students to help their teams with the business side of the process and implement the knowledge they already gained through their studies into this real life experience. Impact entrepreneurship is the kind of entrepreneurship that we are encouraging and supporting at Sofaer,” said Jackie Goren, Head of the Program and one of the mentors at the hackathon. 

Student Initiative

The students who launched the ambitious initiative were Tom Zukerman, Yael Lieber and Orr Erlich – all third-year medical students, and Ilan Peerutin, a third-year dual B.sc Biomedical Engineering, Biology and Neuroscience student.

Together, the four recruited support from international tech and biomedical engineering giants, as well as hospitals and health care funds. Noteworthy sponsors included: The Massachusetts Institute of Technology, AWS, Meuhedet, Sackler Faculty of Medicine, TAU’s Entrepreneurship Center, Teva, Ichilov Tech, Novartis, Startup Nation Central, Philips and the Sagol Center for Regenerative Medicine.

Tel Aviv University encourages entrepreneurial activities for and by its students, and Prof. Karen Avraham, TAU’s Dean of Medicine, supported the students throughout the process: “This was an incredible initiative, and it came entirely from the students. They asked me if the Faculty of Medicine would support the project, and I immediately agreed (…) This hackathon is particularly thrilling because it is not a given that students would dedicate their time and make the effort required to mobilize so many stakeholders to come up with solutions to save people’s lives and health,” she said. 

And the Winners Are… 

Making the Operating Room Safer

The first prize went to team “OReye” from the Clalit Health Services’ general surgery challenge. Most aspects of patient safety in surgeries today are handled solely by the operating team. OReye utilizes cutting-edge computer vision technology to alleviate some of this responsibility, allowing the team to focus solely on the procedure. OReye’s mission is to improve patient safety in the operating room and reduce stress for surgical teams, making it a valuable tool in the operating room. Their project stood out for its originality, feasibility, and potential impact. 

The winning team will be flying to compete in the renowned Massachusetts Institute of Technology (MIT) medical hackathon competition “MIT Grand Hack,” scheduled for April 2023.

The team will also receive an AION Labs and Sanara Ventures accelerator package, which includes personal mentoring hours with experts, office space and professional tools to help develop their winning idea into a commercial startup.

 

The winning team and Prof. Karen Avraham (from left to right): Adi Sarig, Aviv Ziv, Prof. Karen Avraham, Idan Hezler, Eden Elbaz, Raz Naveh and Daphne Cavanaugh

Early Detection of Peripartum Depression

The runner-ups were the “Mommies,” who competed in the women’s health challenge from the Briah Foundation. The team created a community-based wellness app for the early diagnose and treatment of peripartum depression. “It is a true delight to create something for women,” says team member Juliana Gordon from the Sofaer MBA Program, and adds “This is just the beginning. Hopefully we will be able to impact millions of lives, benefitting society.” 

The team will receive ten mentoring sessions with experts from Weccelerate and the Israeli Leumit Health Services.

 

Team “Mommies” with Alon Pinhas from Weccelerate (from left to right): Juliana Gordon, Victoria Koval, Assaf Gadish, Mirit Halfon, Tal Beit Halevi, Shani Zach and Alon Pinhas (Weccelerate)

Personalized Treatment Plans for Breast Reduction 

Team “ABC3D” competed in the Tel Aviv Sourasky Medical Center Ichilov’s plastic surgery challenge. They developed a service that uses 3D models to create personalized treatment plans for breast reduction surgery. This enables advanced prediction and visualization ahead of surgery.

The team was awarded an entrance ticket to the JumpTAU accelerator program at TAU’s Entrepreneurship Center.

 

Team “ABC3D” with Yair Sakov, Head of TAU Entrepreneur Center (from left to right): Savion Cohen, Sarah Tannenbaum, Alaa Masarwa, Ido Shapira, Lydia Sokolovski and Yair Sakov (TAU Entrepreneur Center)

In addition, all the winning teams will receive legal advice, courtesy of leading Israeli commercial law firm Barnea Jaffa Lande.
 

“Prizes for such hackathons are usually monetary,” notes organizer Tom Zuckerman. “However, it was important to us that the winners receive tools and assistance to develop the skillsets needed to advance their initiatives.”

The Joy of the Process

How do the organizers summarize the event? The hackathon exceeded all their expectations: When we started this project, we didn’t imagine that so many people would believe in our vision. Those 40 hours were incredible; 200 talented and motivated students, accompanied by professionals and super-experienced mentors, and an extraordinary panel of judges. Seeing the results was fantastic, but following the process was an absolute joy.”

“We are already looking forward to next year’s hackathon, where we will continue to push the boundaries of medical innovation and positively impact the healthcare industry. In addition, we will be organizing other events during the year, and you’re all welcome to follow us to stay up to date!”

 

Tired but happy. TAU MEDTech organizers (from left to right) Tom Zuckerman, Orr Erlich, Yael Lieber and Ilan Peerutin

Researchers use Smartwatches to Measure Safety of COVID Vaccine

Written by AUFTAU on . Posted in Newsroom.

Tel Aviv University researchers monitored the physiological data of close to 5,000 Israelis over two years.

In a first-of-its-kind study, researchers at Tel Aviv University equipped close to 5,000 Israelis with smartwatches and monitored their physiological parameters over two years. Of those monitored, 2,038 received the booster dose of the coronavirus vaccine, allowing the researchers to objectively compare measures before and after the participants took the vaccine, and confirm its safety.

In addition, in collaboration with the Kahn Sagol Maccabi Research & Innovation Center (KSM – the research and innovation institute of the Israeli Maccabi Healthcare Services), the researchers examined the safety of the booster by analyzing the medical files of 250,000 members of Maccabi Health Services anonymously (without identifying details) and with the approval of the Helsinki Committee. From the analysis of this large amount of data, the researchers were able to evaluate the safety of the vaccines from three perspectives: subjectively – what the participant reports, objectively – what the watch detects, and clinically – what the doctor diagnoses.

 

“We saw clear and significant changes after administration of the vaccine (…) and then we saw a return to the participant’s baseline, i.e., the pulse levels after vaccination returned to their previous levels after six days. Hence, our study confirms the safety of the vaccine.” Prof. Dan Yamin

 

Confirming the Safety of the Vaccine

The research was carried out by PhD student Matan Yechezkel under the supervision of Prof. Dan Yamin, Head of the Laboratory for Epidemic Research and led in collaboration with Prof. Erez Shmueli, Head of the Big Data Laboratory, all from The Iby and Aladar Fleischman Faculty of Engineering at Tel Aviv University. Other collaborators were Dr. Tal Patalon and Dr. Sivan Gazit, Director and Deputy Director, respectively, of KSM, as well as Dr. Amichai Painsky and Ms. Merav Mofaz from Tel Aviv University. The results of the research were published in the prestigious journal, Lancet Respiratory Medicine.

As Prof. Yamin explains: “We wanted to test the safety of booster vaccines against the coronavirus. We conducted a large-scale, two-year clinical study during which we equipped 4,698 Israelis with smartwatches. The smartwatches were used to monitor several parameters such as heart rate, variation in heart activity, quality of sleep, number of daily steps taken, and more. In addition, the participants were asked to fill out daily questionnaires about their health status in a customized application that we developed. Finally, we analyzed data on potential unusual events from the medical files of a quarter of a million randomly selected, anonymous, insured members of the Maccabi Health Services.”

Since the medical file contains the date the booster vaccine was administered, researchers were able to compare the condition of the vaccinated patient with his/her baseline condition from 42 days before receiving the vaccine to the condition of 42 days after receiving the vaccine. The data was obtained from the questionnaires, smartwatches, and records of the Maccabi Health Fund.

 

Prof. Dan Yamin

“We saw clear and significant changes after administration of the vaccine, such as an increase in heart rate compared to the pulse rate measured before vaccination,” says Prof. Yamin, “and then we saw a return to the participant’s baseline, i.e., the pulse levels after vaccination returned to their previous levels after six days. Hence, our study confirms the safety of the vaccine.”

“The research also allowed us to compare subjective and objective indicators and medical diagnosis of the same participant who received the first booster and a few months later the second booster,” explains Prof. Yamin and adds, “We found no difference in the physiological response recorded by the smartwatches and that reported by the participant in the app.”

 

“The smartwatch sensors ‘felt’ that the vaccine was safe, the vaccinee himself reported that the vaccine was safe, and finally, the doctors determined that the vaccine was safe. The results of the study have far-reaching implications regarding objective testing of vaccine safety in the future.” Prof. Dan Yamin

 

Far-reaching Implications

In the medical literature, twenty-five unusual side effects attributed to the Corona vaccine were reported, and the researchers paid special attention to look for rare cases of inflammation of the heart muscle (myocarditis) and pericarditis. Prof. Yamin and his colleagues checked the frequency of these unusual side effects among a quarter of a million Maccabi members and found no increase in serious incidents of any kind associated with vaccination.

Prof. Yamin concludes: “If the watch reports any minor changes in the muscles, and the participant reports only significant changes he feels, the medical file tells us about unusual events diagnosed by the doctors as well as hospitalizations that may be related to vaccinations, with an emphasis on cardiac events. We did a comprehensive analysis of all those twenty-five unusual side effects, and we did not see an increase in their incidence among those receiving the booster. We found the vaccine to be safe to use. The smartwatch sensors ‘felt’ that the vaccine was safe, the vaccinee himself reported that the vaccine was safe, and finally, the doctors determined that the vaccine was safe. The results of the study have far-reaching implications regarding objective testing of vaccine safety in the future.”

Tel Aviv University Establishes Multidisciplinary Center for Research of Autoimmune Diseases

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New center enabled by a generous gift of $10 million from Judith and Stewart Colton

Tel Aviv University has established the Colton Center, Israel’s first multidisciplinary center for the study of autoimmune diseases – chronic conditions involving an abnormal response of the immune system within body tissues. The Center will collaborate with Israel’s medical centers and health services including HMO’s and Hospitals as well as selected scientists from other academic institutions to enable big data analytics of medical information and biological samples from patients with autoimmune diseases and promote understanding of the causes of morbidity and recurrent flareups and possible early diagnostics and treatments.

The TAU research approach will be unique in its nature fundamentally being based on big data analytics that will direct any traditional scientific wet lab work. The intent of the center would be to grant research funding to multidisciplinary groups of scientists including computer science, engineering, biology, statistics, mathematics, psychology, and more. The different research programs will be managed based on agreed upon milestones with the ability to reach substantial sums upon success. In addition to its multidisciplinary clinical research, the new Center will encourage experimental and theoretical studies in immunology and conduct workshops and conferences jointly with the three other Colton Centers.

Goal: Finding a Cure for Autoimmune Diseases

The Center’s establishment was enabled by a generous donation of $10 million from TAU Governors Judith and Stewart Colton. It is the fourth research center founded by the Colton family to address autoimmune diseases, joining three centers already operating in the USA – at Yale University, the University of Pennsylvania, and NYU.

“Stewart and Judith Colton, renowned Jewish philanthropists and dear friends of TAU, have set themselves a goal,” explains Prof. Ariel Porat, President of TAU. This goal is “to develop drugs and treatments for autoimmune diseases. For this purpose, they have established dedicated centers at three leading American universities, and now decided to extend this activity to TAU.”

“This donation is following many years of active contribution by the Colton Foundation to TAU’s innovation and entrepreneurships in wide range of disciplines. We are proud to belong to this elite group of universities, and together with them and the Colton family, we will strive to find a cure for autoimmune diseases.”

 

“Even though autoimmune diseases have been known to science since the beginning of the 20th century, we still don’t have adequate tools for prevention, treatment, or prediction of morbidity and recurrent flareups.” Mr. Stewart Colton

 

Tel Aviv University 

In Need of Adequate Tools

Mr. Stewart Colton comments: “We believe the Consortium created by the four universities will multiply the opportunities for advancing the chances for successful research. We have worked with TAU for almost 40 years and recognize the unique talent and dedication brought to innovative science. It is a terrible disease that deserves more attention.”

“I am particularly proud that Prof. Uri Nevo from the Department of Biomedical Engineering, who was one of the Colton Fellow graduates, was appointed to be the Chair of the Center’s Steering Committee.”

“The category of autoimmune diseases covers over 100 diseases, with relatively familiar examples including lupus, multiple sclerosis (MS), psoriasis, and Crohn’s disease.  Autoimmune diseases are defined as diseases in which the immune system, instead of pathogens such as viruses and bacteria, or cells infected with these pathogens, attack the body’s healthy tissues. Even though autoimmune diseases have been known to science since the beginning of the 20th century, we still don’t have adequate tools for prevention, treatment, or prediction of morbidity and recurrent flareups.”

 

“The new Colton Center represents the best of basic and translational research – a true collaboration between researchers and clinicians to explore the optimal avenues for deciphering the mechanisms and therapy for autoimmune diseases.” Prof. Karen Avraham

 

True Collaboration Between Researchers and Clinicians

Prof. Karen Avraham, Dean of TAU’s Sackler Faculty of Medicine adds: “the new Colton Center represents the best of basic and translational research – a true collaboration between researchers and clinicians to explore the optimal avenues for deciphering the mechanisms and therapy for autoimmune diseases.”

 

“We will start our research carefully and modestly, hoping that from the focused study we will learn about the basic principles underlying autoimmune diseases, and eventually impact the understanding of many of these diseases, and benefit vast numbers of patients.” Prof. Uri Nevo

 

Aim to Benefit Vast Numbers of Patients

Prof. Uri Nevo from the Department of Biomedical Engineering, Chair of the Center’s Steering Committee, explains that the Center’s purpose is to promote the study and understanding of autoimmune diseases in order to improve their prevention and treatment. The first goal, he says, is to obtain measurable results, identify early signs and develop predictive algorithms for both initial onset and recurrent flare-ups. Eventually, studies may provide explanations, and possibly even discover the cause.

Other goals are to define practical recommendations for preventing onset and recurrence or reducing severity, and acquire new insights about disease mechanisms, enabling the development of new treatment strategies in the future.

Prof. Nevo: “Due to the complexity of the immune system, and the difficulty in measuring the interaction between the immune system and tissues in the body, we face some tough challenges. We do not understand the biological mechanism that drives many autoimmune diseases, or how they are connected with genetic and environmental risk factors. As a result, very few specific medications are on offer, and in many cases the disease becomes chronic.

“One of our main objectives is to establish research collaborations with various players: the medical institutions affiliated with TAU, the health services, and representatives of NPOs addressing the various diseases. Our intention is to sample their data and utilize the vast knowledge they have accumulated. The data will enable computerized analysis of samples taken from autoimmune patients in Israel, to help us understand the causes for the onset and recurrent flareups of these diseases.”

To choose the focus of its research for the next few years, the Colton Center is presently sending out a dedicated survey to thousands of clinicians and researchers in Israel. “We want to hear the opinions of doctors and experts, in order to focus on a limited number of diseases,” says Prof. Nevo. “We will start our research carefully and modestly, hoping that from the focused study we will learn about the basic principles underlying autoimmune diseases, and eventually impact the understanding of many of these diseases, and benefit vast numbers of patients.”

Featured image: Mr. and Mrs. Colton

Breakthrough in the Field of Controlled Drug Delivery

Written by AUFTAU on . Posted in Newsroom.

Tel Aviv University researchers develop new technology for efficient encapsulation and release of biomaterials.

In a world first, researchers found a way to control the encapsulation and release of molecules by exposure to UV light. The technology will advance the development of controlled release delivery systems for drugs and biomaterials.

Efficient encapsulation of molecules is considered a major technological challenge. The new technology, which allows for efficient encapsulation and high loading capacity of molecules, might address this need. The researchers estimate that the technology will lead to further development of delivery systems for controlled release of biomolecules and drugs in the body by external stimuli, using light.

Inspired by Measles

The research was led by PhD student Itai Katzir and supervised by Dr. Ayala Lampel from Shmunis School of Biomedicine and Cancer Research at The George S. Wise Faculty of Life Sciences at Tel Aviv University The study was published in the prestigious journal “Advanced Materials”.

The researchers explain that the new technology is inspired by viral compartments formed by the measles virus. Following infection of the host cell, the virus forms compartments that host all the reactions involved in the formation of new viral particles, a process which gives these compartments their name: viral factories. Recent studies show that these viral factories are in fact dynamic and liquid-like structures that are formed inside the host cell through a process called liquid-liquid phase separation.

Inspired by the viral protein, which is responsible for the formation of these factories, the researchers designed a “peptide” (= a short minimalistic protein) which forms compartments that resemble viral factories for encapsulation of biomolecules.

In addition, the researchers incorporated a unique element to the peptide sequence that enables a control of the encapsulation and release of molecules by irradiating the compartments using UV light.

 

“This technology opens opportunities for biomedical and biotechnological applications including encapsulation, delivery and release of drugs, protein, antibodies or other therapeutic molecules.” Dr. Ayala Lampel

 

Opens Opportunities for Biomedical and Biotechnological Applications

“Our goal was to engineer liquid-like compartments from a complex of peptide and RNA molecules that will enable efficient encapsulation of various biomolecules while keeping their native structure,” explains Dr. Lampel.

“The designed peptide and RNA form liquid-like compartments that resemble viral factories. We further developed these compartments to be stimuli-responsive by incorporating a protecting group to the peptide sequence that is cleaved following UV irradiation. The peptide with the photocleavable protecting group forms compartments with RNA, that have higher encapsulation efficiency for various molecules compared to compartments without the protecting group. We showed that by exposing the compartments to UV light and releasing the protecting group, we can control the release of encapsulated biomolecules.”

“Another unique property of this system is the high permeability and loading capacity of the encapsulated molecules, which is limited in part of the current technologies,” adds Dr. Lampel. “Thus, this technology opens opportunities for biomedical and biotechnological applications including encapsulation, delivery and release of drugs, protein, antibodies or other therapeutic molecules.”

Featured image: Dr. Ayala Lampel from TAU’s Shmunis School of Biomedicine and Cancer Research

Common Medications May Reduce Risk of Metastases after Colon and Rectal Cancer

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Existing drugs to prevent anxiety, stress reactions and inflammation reduced the risk of the spread of cancer metastases after surgery to remove a colon tumor by tens of percent.

Although surgery to remove primary tumors is the mainstay of all cancer treatments, the risk of metastases after tumor removal is estimated at 35% among colon cancer patients, with higher risk in patients with more advance stages of the disease. However, a short, simple, and safe drug treatment developed at Tel Aviv University reduced the risk of the spread of cancer metastases after surgery to remove the primary tumor – according to the first clinical study of its kind conducted among 34 colon cancer patients operated on at Sheba Tel Hashomer Medical Center.

The research was led by Prof. Shamgar Ben-Eliyahu of TAU’s Sagol School of Neuroscience and School of Psychological Sciences at the Gershon H. Gordon Faculty of Social Sciences and Prof. Oded Zamora of TAU’s Sackler Faculty of Medicine, and its results were published in the European Journal of Surgical Oncology. At the same time, an overview of the theory and principles underlying the research was published in Nature Review Cancer.

“The stress during the waiting period for surgery, the stress and inflammation reactions that the body produces during the surgery itself and the physical recovery period, and finally the following anxiety of cancer recurring – all have an adverse effect on the body’s ability to fight metastatic processes,” explains Prof. Ben-Eliyahu. “These mental and physiological conditions create stress-inflammatory responses, which cause ample release of hormones from the prostaglandin and catecholamine families. These hormones suppress anti-metastatic immune activity, and thus encourage the development of metastases.”

“In addition, these hormones directly help the cancer cells that remain in the body even after surgery: due to exposure to these hormones, the cancerous tissue becomes more aggressive and metastatic. The good news is that we know how to treat both stress and inflammation using off-the-shelf medications.”

 

“This is a short, cheap drug treatment with no significant side effects. We deliberately sought the safest and cheapest drugs capable of lowering the body’s stress-inflammatory response to surgery, in order to save lives.” Prof. Shamgar Ben-Eliyahu

 

Significant and Encouraging Results

The researchers from Tel Aviv University gave 34 colon cancer patients two safe drugs that are available in every pharmacy: propranolol (Darlin), used to lower blood pressure and reduce anxiety, and etodolac (Etopan), used to prevent pain and inflammation.

Sixteen randomly chosen patients took the medication for 20 days – from five days before to two weeks after surgery at the Sheba Medical Center. The other 18 patients received placebo drugs (control group). Five years later, nine of the 18 patients who received the placebo (50%) developed cancer metastases, compared to two of the 16 patients who took Darlin and Etofen (12.5%).

“Although at five years after the operation, the statistical significance is clear, we need to conduct larger clinical studies,” says Prof. Ben-Eliyahu. “Our treatment reduced markers of metastasis in the tumor tissue and reduced the chances of cancer recurrence. This is a short, cheap drug treatment with no significant side effects. We deliberately sought the safest and cheapest drugs capable of lowering the body’s stress-inflammatory response to surgery, in order to save lives.”

“It sounds too good to be true, but similar results in breast cancer tissue were obtained in a study we conducted in 2017. Due to the small number of subjects in both studies, it is impossible to accurately estimate the magnitude of the beneficial effect, but the effects are statistically significant, meaning that they are not accidental.”

 

“We seek to save lives without financial gain, and we have received financial support from several Israeli and international sources, but these are insufficient for large clinical studies.” Prof. Shamgar  Ben-Eliyahu

 

Saving Lives Without Financial Gain

According to Prof. Ben-Eliyahu, part of the medical establishment distrusts the effects of stress-inflammatory reactions, particularly those resulting from psychological factors such as waiting for surgery or fear of the disease spreading. Another problem concerns the financing of clinical studies.

“One should bear in mind that the pharmaceutical companies have no financial incentive to support such studies. Our medicines are not patented; they are safe, cheap, and administered in a short treatment lasting just a few days. The drug companies look for patents on expensive drugs and prefer that the patient be dependent on the drug for the rest of their life.”

“Unfortunately, the major science foundations in Israel do not fund clinical research on drugs, assuming that the drug companies will fund them. We seek to save lives without financial gain, and we have received financial support from several Israeli and international sources, but these are insufficient for large clinical studies. I hope that funding will be found for a large-scale clinical study that we have now embarked on, with the intention of recruiting hundreds of colon and rectal cancer patients in Israel, because without such research – we will not be able to convince the medical establishment of the treatment’s effectiveness.”

The Superpowers of the Female Locust

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She can stretch up to 2-3 times her original length when laying eggs in the ground, without causing irreparable damage.

Every mother will do anything to know that her offspring are in a safe place. The female locust, however, takes it to a whole new level: A new Tel Aviv University study has discovered that these females have superpowers. The female locust’s central nervous system has elastic properties, allowing her to stretch up to two or three times her original length when laying her eggs in the ground, without causing any irreparable damage.

“We are not aware of a similar ability in almost any living creature,” say the researchers. “Nerves in the human nervous system, for example, can stretch only up to 30% without tearing or being permanently damaged. In the future, these findings may contribute to new developments in the field of regenerative medicine, as a basis for nerve restoration and the development of synthetic tissues.”

 

“The superpower of the locust is almost something out of science fiction. There are only two other known examples in nature of a similar phenomenon: the tongue of the sperm whale, and a certain type of sea snail whose nervous systems are able to extend significantly due to an accordion-like mechanism they have.” Prof. Amir Ayali

 

WATCH: TAU Researchers Describe their Surprising Discovery – The Female Locust has Superhero-like Abilities

 

Showing Flexibility

The study was conducted by a team of Tel Aviv University researchers led by Dr. Bat-El Pinchasik of the School of Mechanical Engineering in The Iby and Aladar Fleischman Faculty of Engineering and Prof. Amir Ayali of the School of Zoology in the George S. Wise Faculty of Life Sciences. Also participating in the study were Dr. Rakesh Das from the School of Mechanical Engineering, Dr. Moshe Guershon from the School of Zoology, and Prof. Eran Perlson and Amjd Ibraheem from the Department of Physiology and Pharmacology in the Sackler Faculty of Medicine. The research was published in iScience.

“When the female locust is ready to lay her eggs, she digs a hole in the ground that will offer them protection and optimal conditions for hatching,” explains Dr. Pinchasik. “For this purpose, she is equipped with a unique digging apparatus, consisting of two pairs of digging valves located at the tip of the abdomen, on either side of the ovipositor (a tube-like organ used for laying eggs).”

“As she digs, she extends her body, until sensors located along its length signal that she has reached a suitable point for depositing her eggs. Thus, an adult female, whose body length is about four to five centimeters, may, for the purpose of laying her eggs, stretch her body to a length of 10-15 centimeters, then quickly return to her normal length, and then extend again for the next egg-laying.”

“The superpower of the locust is almost something out of science fiction,” muses Prof. Ayali. “There are only two other known examples in nature of a similar phenomenon: the tongue of the sperm whale, and a certain type of sea snail whose nervous systems are able to extend significantly due to an accordion-like mechanism they have. We sought to identify the biomechanical mechanism that gives the female locust its wonderful ability.”

 

From left to right: Prof. Amir Ayali, Dr. Rakesh Das and Dr. Bat-El Pinchasik

 

“Contrary to previous hypotheses and examples we are familiar with, we did not find any accordion-like mechanism. We discovered that the nervous system of the female locust has elastic properties, which enable it to elongate and then return by itself to its original state, ready for reuse, without any damage caused to the tissue. This finding is almost incomprehensible from a biomechanical and morphological point of view.” Dr. Bat-El Pinchasik

 

Key to Rehabilitation Treatments and Regenerative Medicine?

In the study, the researchers removed the central nervous systems from female locusts and placed them in a liquid simulating their natural environment, under physiological conditions similar to those inside the body. Using highly sensitive measuring instruments, they measured the forces needed to extend the nervous system.

Dr. Pinchasik: “Contrary to previous hypotheses and examples we are familiar with, we did not find any accordion-like mechanism. We discovered that the nervous system of the female locust has elastic properties, which enable it to elongate and then return by itself to its original state, ready for reuse, without any damage caused to the tissue. This finding is almost incomprehensible from a biomechanical and morphological point of view.”

Prof. Ayali adds that, “in further studies, we will investigate the matter in depth, with the aim of identifying the specific mechanism that enables this unique feature. We hope that in the future our findings will help to develop synthetic tissues with a high level of flexibility, and to restore nerves in regenerative medicine therapies.”

Are Today’s Gynecologists Ignoring Women’s Health Issues?

Written by AUFTAU on . Posted in Newsroom.

Women’s health and wellbeing receive little attention compared to childbirth and reproduction, both in research and in clinic.

A new preliminary study from Tel Aviv University reveals that due to masculine dominance of the gynecological science field, most gynecological research focuses on childbirth and reproduction rather than women’s health and wellbeing. Mapping scientific journals in the category of gynecology and obstetrics, the study found that the majority deal with fertility, pregnancy, fetuses, and childbirth, while many topics that are much more critical to women’s quality of life receive little attention, both in scientific research and in the clinic.

The study was conducted by Dr. Netta Avnoon of the Department of Sociology and Anthropology and the Coller School of Management at Tel Aviv University. The preliminary results were published in the prestigious journal Nature Reviews Urology

 

“Men have dominated gynecology for almost a thousand years, and their gender identity impacts everything that happens in this specialty, including research design and medical practices.” Dr Netta Avnoon

 

Male Dominated Discipline

According to the preliminary study important issues that have been marginalized for centuries include diseases and damage to the muscles and nerves of the female pelvis and sexual organs, female sexual pleasure, rights and autonomy in childbirth, the connection between the menstrual cycle and the immune system, menopause, and the later years of life, and more.

“Men have dominated gynecology for almost a thousand years, and their gender identity impacts everything that happens in this specialty, including research design and medical practices,” says Dr. Avnoon. “Even if they are unaware of their own bias and have the best intentions, men traditionally regard the female body as an object for producing babies or satisfying men’s sexual desires. The time has come for women to dominate the discipline that is meant to care for their health.”

Dr. Avnoon explains that no social activity is neutral, objective or contextless, and science and medicine are no exception. Inevitably, social positions and dispositions impact the attitudes of those who create science.

Extensive historical and feminist scholarship has shown that gynecology as a medical specialty was masculinized 800 years ago, and still adheres to patriarchal values. In ancient times women were usually treated by women-experts, who even wrote books on the subject, but during the Middle Ages, these women and their knowledge were gradually ousted and replaced by men.

Since the 16th century the specialty has been wholly dominated by males, and consequently they were the ones to determine which topics are ‘interesting’ and worth studying; they were the ones who set practices and protocols and introduced treatments, technologies, and techniques, all too often subjecting patients to medical practices that are not necessarily benevolent.

 

Dr. Netta Avnoon

Exposing Current Focus

To expose the actual focus of gynecological research today, in line with previous feminist studies, Dr. Avnoon chose a tell-tale indicator: the titles of international scientific journals in the ‘gynecology and obstetrics’ category.

She analyzed the list appearing in the Journal Citation Reports, a database that provides general and statistical information about scientific journals worldwide, and the results were clear-cut: of the 83 journals listed by title in the category, 49% are dedicated solely to reproductive functions, pregnancy, fetuses, and childbirth; 24% focus on both gynecology and obstetrics; only 12% deal with health issues in the female sexual organs that are unrelated to reproductive functions; 6% deal with breasts; 5% deal with gynecological cancers; and a mere 4% (3 journals) address the health of women before and after childbearing age, including menopause.

Dr. Avnoon notes a recent instance of gynecology’s gender bias: the transvaginal mesh scandal. In 2019 the FDA banned the use of the transvaginal mesh – a common gynecological procedure used since the 1950s to repair pelvis organ prolapse in the anterior vaginal compartment, which had caused extensive morbidity and even 77 documented deaths in the USA.

Patients’ activism moved the regulator to intervene, exposing the decades-long failure of gynecological science to clinically assess the outcomes of this surgical procedure, and revealing the bias in how researchers presented these results in scientific publications.

 

“Care for the fetus, essential in its own right, must not come at the expense of the mother’s health.” Dr. Netta Avnoon

 

It’s Time: Women-Centered Gynecology

What solution does Dr. Avnoon have in mind? She proposes the following: “Obstetrics, focusing on fertility, reproduction, pregnancy, the fetus and childbirth, should be separated from gynecology, a specialty dedicated to women’s health.”

“Care for the fetus, essential in its own right, must not come at the expense of the mother’s health.”

“Also, gynecology training must include a major chapter of gender and feminist studies, and existing medical protocols should be amended to focus on the needs of the women – rather than those of their babies, their spouses, or their doctors. Moreover, legislation and legal procedures are in order, especially in courts of human rights, to protect women’s right to health and optimal medical care.”

“The time has come for women-centered gynecology,” says Dr. Avnoon. “Women’s voices must be heard.”

“To date, medical schools offer their students very scant and unsatisfactory knowledge about female anatomy and physiology, specifically in terms of women’s sexuality. Even though the overall numbers of female gynecologists are on the rise (in the US there are by now more women than men in this profession), their education is still based on age-old masculine and chauvinistic traditions.”

“In order to generate real change, doctors must be trained to regard women’s rights, health, and sexuality as the focus of women’s medicine, and to treat their patients with respect. Greater emphasis should be given to patient experience and autonomy in medical settings, and to much-needed innovation in research, instruments, technologies, protocols, surgical procedures, and medications.”

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